Properties and prospects of adjuvants in influenza vaccination - messy precipitates or blessed opportunities?

  • Babak Jalilian Biophysical Immunology Laboratory, Department of Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark
  • Stig Christiansen Biophysical Immunology Laboratory, Department of Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark
  • Halldór Einarsson Biophysical Immunology Laboratory, Department of Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark
  • Mehdi Pirozyan Biophysical Immunology Laboratory, Department of Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark
  • Eskild Peterson Biophysical Immunology Laboratory, Department of Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark
  • Thomas Vorup-Jensen
Keywords: Adjuvants, Influenza vaccination, Particle size

Abstract

Influenza is a major challenge to healthcare systems world-wide. While prophylactic vaccination is largely efficient, long-lasting immunity has not been achieved in immunized populations, at least in part due to the challenges arising from the antigen variation between strains of influenza A virus as a consequence of genetic drift and shift. From progress in our understanding of the immune system, the mode-of-action of vaccines can be divided into the stimulation of the adaptive system through inclusion of appropriate vaccine antigens and of the innate immune system by the addition of adjuvant to the vaccine formulation. A shared property of many vaccine adjuvants is found in their nature of water-insoluble precipitates, for instance the particulate material made from aluminum salts. Previously, it was thought that embedding of vaccine antigens in these materials provided a “depot” of antigens enabling a long exposure of the immune system to the antigen. However, more recent work points to a role of particulate adjuvants in stimulating cellular parts of the innate immune system. Here, we briefly outline the infectious medicine and immune biology of influenza virus infection and procedures to provide sufficient and stably available amounts of vaccine antigen. This is followed by presentation of the many roles of adjuvants, which involve humoral factors of innate immunity, notably complement. In a perspective of the ultrastructural properties of these humoral factors, it becomes possible to rationalize why these insoluble precipitates or emulsions are such a provocation of the immune system. We propose that the biophysics of particulate material may hold opportunities that could aid the development of more efficient influenza vaccines.

Downloads

Download data is not yet available.

Author Biography

Thomas Vorup-Jensen

Biophysical Immunology Laboratory, Department of Biomedicine, Aarhus
University, DK-8000 Aarhus, Denmark

References

Janeway CA: Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harbor symposia on quantitative biology. 1989, 54 (Pt 1): 1-13.

PubMedGoogle Scholar

Bridges CB, Kuehnert MJ, Hall CB: Transmission of influenza: implications for control in health care settings. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2003, 37: 1094-1101. 10.1086/378292.

Google Scholar

Lessler J, Reich NG, Brookmeyer R, Perl TM, Nelson KE, Cummings DA: Incubation periods of acute respiratory viral infections: a systematic review. The Lancet infectious diseases. 2009, 9: 291-300. 10.1016/S1473-3099(09)70069-6.

PubMedCentralPubMedGoogle Scholar

Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR: Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. American journal of epidemiology. 1998, 148: 1094-1102. 10.1093/oxfordjournals.aje.a009587.

PubMedGoogle Scholar

Barker WH, Mullooly JP: Pneumonia and influenza deaths during epidemics: implications for prevention. Archives of internal medicine. 1982, 142: 85-89. 10.1001/archinte.1982.00340140087016.

PubMedGoogle Scholar

Lin JC, Nichol KL: Excess mortality due to pneumonia or influenza during influenza seasons among persons with acquired immunodeficiency syndrome. Archives of internal medicine. 2001, 161: 441-446. 10.1001/archinte.161.3.441.

PubMedGoogle Scholar

Kwong JC, Campitelli MA, Rosella LC: Obesity and respiratory hospitalizations during influenza seasons in Ontario, Canada: a cohort study. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2011, 53: 413-421. 10.1093/cid/cir442.

Google Scholar

Finelli L, Fiore A, Dhara R, Brammer L, Shay DK, Kamimoto L, Fry A, Hageman J, Gorwitz R, Bresee J, Uyeki T: Influenza-associated pediatric mortality in the United States: increase of staphylococcus aureus coinfection. Pediatrics. 2008, 122: 805-811. 10.1542/peds.2008-1336.

PubMedGoogle Scholar

Rothberg MB, Haessler SD, Brown RB: Complications of viral influenza. The American journal of medicine. 2008, 121: 258-264. 10.1016/j.amjmed.2007.10.040.

PubMedGoogle Scholar

Petersen E, Keld DB, Ellermann-Eriksen S, Gubbels S, Ilkjaer S, Jensen-Fangel S, Lindskov C: Failure of combination oral oseltamivir and inhaled zanamivir antiviral treatment in ventilator- and ECMO-treated critically ill patients with pandemic influenza A (H1N1)v. Scandinavian journal of infectious diseases. 2011, 43: 495-503. 10.3109/00365548.2011.556144.

PubMedGoogle Scholar

Rohde G, Wiethege A, Borg I, Kauth M, Bauer TT, Gillissen A, Bufe A, Schultze-Werninghaus G: Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case–control study. Thorax. 2003, 58: 37-42. 10.1136/thorax.58.1.37.

PubMedCentralPubMedGoogle Scholar

Mamas MA, Fraser D, Neyses L: Cardiovascular manifestations associated with influenza virus infection. International journal of cardiology. 2008, 130: 304-309. 10.1016/j.ijcard.2008.04.044.

PubMedGoogle Scholar

Warren-Gash C, Smeeth L, Hayward AC: Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review. The Lancet infectious diseases. 2009, 9: 601-610. 10.1016/S1473-3099(09)70233-6.

PubMedGoogle Scholar

Murray PR, Rosenthal KS, Pfaller MA: Medical Microbiology. 2013, Oxford: Elsevier Saunders, 7

Google Scholar

Guo YJ, Jin FG, Wang P, Wang M, Zhu JM: Isolation of influenza C virus from pigs and experimental infection of pigs with influenza C virus. J Gen Virol. 1983, 64 (Pt 1): 177-182.

PubMedGoogle Scholar

Osterhaus AD, Rimmelzwaan GF, Martina BE, Bestebroer TM, Fouchier RA: Influenza B virus in seals. Science. 2000, 288: 1051-1053. 10.1126/science.288.5468.1051.

PubMedGoogle Scholar

Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y: Evolution and ecology of influenza A viruses. Microbiological reviews. 1992, 56: 152-179.

PubMedCentralPubMedGoogle Scholar

Tong S, Li Y, Rivailler P, Conrardy C, Castillo DA, Chen LM, Recuenco S, Ellison JA, Davis CT, York IA: A distinct lineage of influenza A virus from bats. Proc Natl Acad Sci USA. 2012, 109: 4269-4274.

PubMedCentralPubMedGoogle Scholar

Harris A, Cardone G, Winkler DC, Heymann JB, Brecher M, White JM, Steven AC: Influenza virus pleiomorphy characterized by cryoelectron tomography. Proc Natl Acad Sci USA. 2006, 103: 19123-19127. 10.1073/pnas.0607614103.

PubMedCentralPubMedGoogle Scholar

Mitnaul LJ, Matrosovich MN, Castrucci MR, Tuzikov AB, Bovin NV, Kobasa D, Kawaoka Y: Balanced hemagglutinin and neuraminidase activities are critical for efficient replication of influenza A virus. Journal of virology. 2000, 74: 6015-6020. 10.1128/JVI.74.13.6015-6020.2000.

PubMedCentralPubMedGoogle Scholar

Zhang Y, Lin X, Wang G, Zhou J, Lu J, Zhao H, Zhang F, Wu J, Xu C, Du N: Neuraminidase and hemagglutinin matching patterns of a highly pathogenic avian and two pandemic H1N1 influenza A viruses. PloS one. 2010, 5: e9167-10.1371/journal.pone.0009167.

PubMedCentralPubMedGoogle Scholar

Gjelstrup LC, Kaspersen JD, Behrens MA, Pedersen JS, Thiel S, Kingshott P, Oliveira CL, Thielens NM, Vorup-Jensen T: The role of nanometer-scaled ligand patterns in polyvalent binding by large mannan-binding lectin oligomers. J Immunol. 2012, 188: 1292-1306. 10.4049/jimmunol.1103012.

PubMedGoogle Scholar

Matrosovich MN, Matrosovich TY, Gray T, Roberts NA, Klenk HD: Human and avian influenza viruses target different cell types in cultures of human airway epithelium. Proc Natl Acad Sci USA. 2004, 101: 4620-4624. 10.1073/pnas.0308001101.

PubMedCentralPubMedGoogle Scholar

Stevens J, Blixt O, Tumpey TM, Taubenberger JK, Paulson JC, Wilson IA: Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Science. 2006, 312: 404-410. 10.1126/science.1124513.

PubMedGoogle Scholar

Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y: Avian flu: influenza virus receptors in the human airway. Nature. 2006, 440: 435-436. 10.1038/440435a.

PubMedGoogle Scholar

Calfee DP, Peng AW, Hussey EK, Lobo M, Hayden FG: Safety and efficacy of once daily intranasal zanamivir in preventing experimental human influenza A infection. Antiviral therapy. 1999, 4: 143-149.

PubMedGoogle Scholar

Arndt U, Wennemuth G, Barth P, Nain M, Al-Abed Y, Meinhardt A, Gemsa D, Bacher M: Release of macrophage migration inhibitory factor and CXCL8/interleukin-8 from lung epithelial cells rendered necrotic by influenza A virus infection. Journal of virology. 2002, 76: 9298-9306. 10.1128/JVI.76.18.9298-9306.2002.

PubMedCentralPubMedGoogle Scholar

Lam WY, Yeung AC, Chu IM, Chan PK: Profiles of cytokine and chemokine gene expression in human pulmonary epithelial cells induced by human and avian influenza viruses. Virology journal. 2010, 7: 344-10.1186/1743-422X-7-344.

PubMedCentralPubMedGoogle Scholar

Garcia CC, Weston-Davies W, Russo RC, Tavares LP, Rachid MA, Alves-Filho JC, Machado AV, Ryffel B, Nunn MA, Teixeira MM: Complement C5 activation during influenza A infection in mice contributes to neutrophil recruitment and lung injury. PloS one. 2013, 8: e64443-10.1371/journal.pone.0064443.

PubMedCentralPubMedGoogle Scholar

Burnet FM, Mc CJ: Inhibitory and activating action of normal ferret sera against an influenza virus strain. Aust J Exp Biol Med Sci. 1946, 24: 277-282. 10.1038/icb.1946.41.

PubMedGoogle Scholar

Anders EM, Hartley CA, Jackson DC: Bovine and mouse serum beta inhibitors of influenza A viruses are mannose-binding lectins. Proc Natl Acad Sci USA. 1990, 87: 4485-4489. 10.1073/pnas.87.12.4485.

PubMedCentralPubMedGoogle Scholar

Chang WC, White MR, Moyo P, McClear S, Thiel S, Hartshorn KL, Takahashi K: Lack of the pattern recognition molecule mannose-binding lectin increases susceptibility to influenza A virus infection. BMC immunology. 2010, 11: 64-10.1186/1471-2172-11-64.

PubMedCentralPubMedGoogle Scholar

Job ER, Deng YM, Tate MD, Bottazzi B, Crouch EC, Dean MM, Mantovani A, Brooks AG, Reading PC: Pandemic H1N1 influenza A viruses are resistant to the antiviral activities of innate immune proteins of the collectin and pentraxin superfamilies. J Immunol. 2010, 185: 4284-4291. 10.4049/jimmunol.1001613.

PubMedGoogle Scholar

Vorup-Jensen T: On the roles of polyvalent binding in immune recognition: perspectives in the nanoscience of immunology and the immune response to nanomedicines. Advanced drug delivery reviews. 2012, 64: 1759-1781. 10.1016/j.addr.2012.06.003.

PubMedGoogle Scholar

Gil M, McCormack FX, Levine AM: Surfactant protein A modulates cell surface expression of CR3 on alveolar macrophages and enhances CR3-mediated phagocytosis. The Journal of biological chemistry. 2009, 284: 7495-7504. 10.1074/jbc.M808643200.

PubMedCentralPubMedGoogle Scholar

Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A, Flavell RA: Recognition of single-stranded RNA viruses by toll-like receptor 7. Proc Natl Acad Sci USA. 2004, 101: 5598-5603. 10.1073/pnas.0400937101.

PubMedCentralPubMedGoogle Scholar

McMichael AJ, Gotch FM, Noble GR, Beare PA: Cytotoxic T-cell immunity to influenza. The New England journal of medicine. 1983, 309: 13-17. 10.1056/NEJM198307073090103.

PubMedGoogle Scholar

Wilkinson TM, Li CK, Chui CS, Huang AK, Perkins M, Liebner JC, Lambkin-Williams R, Gilbert A, Oxford J, Nicholas B: Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nature medicine. 2012, 18: 274-280. 10.1038/nm.2612.

PubMedGoogle Scholar

Hardy S, Eichelberger M, Griffiths E, Weir JP, Wood D, Alfonso C: Confronting the next pandemic–workshop on lessons learned from potency testing of pandemic (H1N1) 2009 influenza vaccines and considerations for future potency tests, Ottawa, Canada, July 27–29, 2010. Influenza and other respiratory viruses. 2011, 5: 438-442. 10.1111/j.1750-2659.2011.00250.x.

PubMedGoogle Scholar

Douek DC, McFarland RD, Keiser PH, Gage EA, Massey JM, Haynes BF, Polis MA, Haase AT, Feinberg MB, Sullivan JL: Changes in thymic function with age and during the treatment of HIV infection. Nature. 1998, 396: 690-695. 10.1038/25374.

PubMedGoogle Scholar

Fagnoni FF, Vescovini R, Passeri G, Bologna G, Pedrazzoni M, Lavagetto G, Casti A, Franceschi C, Passeri M, Sansoni P: Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging. Blood. 2000, 95: 2860-2868.

PubMedGoogle Scholar

Rosenberg C: Investigation of the immune responses induced after immunizatuion against the intracellular microorganisms Toxoplasma gondii and Hepatitis B virus (Ph.D. thesis). 2012, Aarhus University, Dept of Biomedicine

Google Scholar

Castle SC: Clinical relevance of age-related immune dysfunction. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2000, 31: 578-585. 10.1086/313947.

Google Scholar

Aspinall R, Andrew D: Thymic involution in aging. Journal of clinical immunology. 2000, 20: 250-256. 10.1023/A:1006611518223.

PubMedGoogle Scholar

Goronzy JJ, Lee WW, Weyand CM: Aging and T-cell diversity. Experimental gerontology. 2007, 42: 400-406. 10.1016/j.exger.2006.11.016.

PubMedCentralPubMedGoogle Scholar

Kang I, Hong MS, Nolasco H, Park SH, Dan JM, Choi JY, Craft J: Age-associated change in the frequency of memory CD4+ T cells impairs long term CD4+ T cell responses to influenza vaccine. J Immunol. 2004, 173: 673-681.

PubMedGoogle Scholar

Rosenberg C, Bovin NV, Bram LV, Flyvbjerg E, Erlandsen M, Vorup-Jensen T, Petersen E: Age is an important determinant in humoral and T cell responses to immunization with hepatitis B surface antigen. Human vaccines & immunotherapeutics. 2013, 9: 1466-1476. 10.4161/hv.24480.

Google Scholar

Effros RB, Boucher N, Porter V, Zhu X, Spaulding C, Walford RL, Kronenberg M, Cohen D, Schachter F: Decline in CD28+ T cells in centenarians and in long-term T cell cultures: a possible cause for both in vivo and in vitro immunosenescence. Experimental gerontology. 1994, 29: 601-609. 10.1016/0531-5565(94)90073-6.

PubMedGoogle Scholar

Vallejo AN: CD28 extinction in human T cells: altered functions and the program of T-cell senescence. Immunological reviews. 2005, 205: 158-169. 10.1111/j.0105-2896.2005.00256.x.

PubMedGoogle Scholar

Weng NP, Akbar AN, Goronzy J: CD28(−) T cells: their role in the age-associated decline of immune function. Trends in immunology. 2009, 30: 306-312. 10.1016/j.it.2009.03.013.

PubMedCentralPubMedGoogle Scholar

Jalilian B, Einarsson HB, Vorup-Jensen T: Glatiramer acetate in treatment of multiple sclerosis: a toolbox of random co-polymers for targeting inflammatory mechanisms of both the innate and adaptive immune system?. International journal of molecular sciences. 2012, 13: 14579-14605. 10.3390/ijms131114579.

PubMedCentralPubMedGoogle Scholar

Cox RJ, Brokstad KA, Ogra P: Influenza virus: immunity and vaccination strategies. Comparison of the immune response to inactivated and live, attenuated influenza vaccines. Scandinavian journal of immunology. 2004, 59: 1-15. 10.1111/j.0300-9475.2004.01382.x.

PubMedGoogle Scholar

Swayne DE, Beck JR: Heat inactivation of avian influenza and Newcastle disease viruses in egg products. Avian Pathol. 2004, 33: 512-518. 10.1080/03079450400003692.

PubMedGoogle Scholar

Matthews JT: Egg-based production of influenza vaccine: 30 years of commercial experience. The Bridge. 2006, 36: 17-24.

Google Scholar

Lambert LC, Fauci AS: Influenza vaccines for the future. The New England journal of medicine. 2010, 363: 2036-2044. 10.1056/NEJMra1002842.

PubMedGoogle Scholar

Singh N, Pandey A, Mittal SK: Avian influenza pandemic preparedness: developing prepandemic and pandemic vaccines against a moving target. Expert reviews in molecular medicine. 2010, 12: e14-

PubMedCentralPubMedGoogle Scholar

Sedova ES, Shcherbinin DN, Migunov AI, Smirnov Iu A, Logunov D, Shmarov MM, Tsybalova LM, Naroditskii BS, Kiselev OI, Gintsburg AL: Recombinant influenza vaccines. Acta naturae. 2012, 4: 17-27.

PubMedCentralPubMedGoogle Scholar

Lin SC, Huang MH, Tsou PC, Huang LM, Chong P, Wu SC: Recombinant trimeric HA protein immunogenicity of H5N1 avian influenza viruses and their combined use with inactivated or adenovirus vaccines. PloS one. 2011, 6: e20052-10.1371/journal.pone.0020052.

PubMedCentralPubMedGoogle Scholar

Nemchinov LG, Natilla A: Transient expression of the ectodomain of matrix protein 2 (M2e) of avian influenza A virus in plants. Protein expression and purification. 2007, 56: 153-159. 10.1016/j.pep.2007.05.015.

PubMedGoogle Scholar

Huleatt JW, Nakaar V, Desai P, Huang Y, Hewitt D, Jacobs A, Tang J, McDonald W, Song L, Evans RK: Potent immunogenicity and efficacy of a universal influenza vaccine candidate comprising a recombinant fusion protein linking influenza M2e to the TLR5 ligand flagellin. Vaccine. 2008, 26: 201-214. 10.1016/j.vaccine.2007.10.062.

PubMedGoogle Scholar

Rasoli M, Omar AR, Aini I, Jalilian B, Syed Hassan SH, Mohamed M: Fusion of HSP70 gene of Mycobacterium tuberculosis to hemagglutinin (H5) gene of avian influenza virus in DNA vaccine enhances its potency. Acta virologica. 2010, 54: 33-39. 10.4149/av_2010_01_33.

PubMedGoogle Scholar

Donnelly J, Friedman A, Ulmer J, Liu M: Further protection against antigenic drift of influenza virus in a ferret model by DNA vaccination. Vaccine. 1997, 15: 865-868. 10.1016/S0264-410X(96)00268-X.

PubMedGoogle Scholar

Donnelly JJ, Friedman A, Martinez D, Montgomery DL, Shiver JW, Motzel SL, Ulmer JB, Liu MA: Preclinical efficacy of a prototype DNA vaccine: enhanced protection against antigenic drift in influenza virus. Nature medicine. 1995, 1: 583-587. 10.1038/nm0695-583.

PubMedGoogle Scholar

Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Felgner PL, Dwarki VJ, Gromkowski SH, Deck RR, DeWitt CM, Friedman A: Heterologous protection against influenza by injection of DNA encoding a viral protein. Science. 1993, 259: 1745-1749. 10.1126/science.8456302.

PubMedGoogle Scholar

Justewicz DM, Morin MJ, Robinson HL, Webster RG: Antibody-forming cell response to virus challenge in mice immunized with DNA encoding the influenza virus hemagglutinin. Journal of virology. 1995, 69: 7712-7717.

PubMedCentralPubMedGoogle Scholar

Donnelly JJ, Ulmer JB, Liu MA: Immunization with DNA. J Immunol Methods. 1994, 176: 145-152. 10.1016/0022-1759(94)90308-5.

PubMedGoogle Scholar

Ulmer JB, Fu TM, Deck RR, Friedman A, Guan L, DeWitt C, Liu X, Wang S, Liu MA, Donnelly JJ, Caulfield MJ: Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination with nucleoprotein DNA. Journal of virology. 1998, 72: 5648-5653.

PubMedCentralPubMedGoogle Scholar

Gomez Lorenzo MM, Fenton MJ: Immunobiology of influenza vaccines. Chest. 2013, 143: 502-510. 10.1378/chest.12-1711.

PubMedCentralPubMedGoogle Scholar

Vogel FR: Improving vaccine performance with adjuvants. Clin Infect Dis. 2000, 30: S266-S270. 10.1086/313883.

PubMedGoogle Scholar

Aucouturier J, Dupuis L, Ganne V: Adjuvants designed for veterinary and human vaccines. Vaccine. 2001, 19: 2666-2672. 10.1016/S0264-410X(00)00498-9.

PubMedGoogle Scholar

de Veer M, Meeusen E: New developments in vaccine research–unveiling the secret of vaccine adjuvants. Discov Med. 2011, 12: 195-204.

PubMedGoogle Scholar

Marrack P, McKee AS, Munks MW: Towards an understanding of the adjuvant action of aluminium. Nat Rev Immunol. 2009, 9: 287-293. 10.1038/nri2510.

PubMedCentralPubMedGoogle Scholar

McCartney S, Vermi W, Gilfillan S, Cella M, Murphy TL, Schreiber RD, Murphy KM, Colonna M: Distinct and complementary functions of MDA5 and TLR3 in poly(I:C)-mediated activation of mouse NK cells. The Journal of experimental medicine. 2009, 206: 2967-2976. 10.1084/jem.20091181.

PubMedCentralPubMedGoogle Scholar

Coffman RL, Sher A, Seder RA: Vaccine adjuvants: putting innate immunity to work. Immunity. 2010, 33: 492-503. 10.1016/j.immuni.2010.10.002.

PubMedCentralPubMedGoogle Scholar

Desmet CJ, Ishii KJ: Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination. Nat Rev Immunol. 2012, 12: 479-491. 10.1038/nri3247.

PubMedGoogle Scholar

Hem SL, Hogenesch H: Relationship between physical and chemical properties of aluminum-containing adjuvants and immunopotentiation. Expert review of vaccines. 2007, 6: 685-698. 10.1586/14760584.6.5.685.

PubMedGoogle Scholar

O’Hagan DT, Ott GS, Nest GV, Rappuoli R, Giudice GD: The history of MF59((R)) adjuvant: a phoenix that arose from the ashes. Expert review of vaccines. 2013, 12: 13-30. 10.1586/erv.12.140.

PubMedGoogle Scholar

Garcon N, Vaughn DW, Didierlaurent AM: Development and evaluation of AS03, an adjuvant system containing alpha-tocopherol and squalene in an oil-in-water emulsion. Expert review of vaccines. 2012, 11: 349-366. 10.1586/erv.11.192.

PubMedGoogle Scholar

de Jonge J, Schoen P, ter Veer W, Stegmann T, Wilschut J, Huckriede A: Use of a dialyzable short-chain phospholipid for efficient solubilization and reconstitution of influenza virus envelopes. Biochimica et biophysica acta. 2006, 1758: 527-536. 10.1016/j.bbamem.2006.03.011.

PubMedGoogle Scholar

Mbow ML, De Gregorio E, Valiante NM, Rappuoli R: New adjuvants for human vaccines. Curr Opin Immunol. 2010, 22: 411-416. 10.1016/j.coi.2010.04.004.

PubMedGoogle Scholar

Rappuoli R, Mandl CW, Black S, De Gregorio E: Vaccines for the twenty-first century society. Nat Rev Immunol. 2011, 11: 865-872.

PubMedGoogle Scholar

Gupta RK, Siber GR: Comparison of adjuvant activities of aluminium phosphate, calcium phosphate and stearyl tyrosine for tetanus toxoid. Biologicals. 1994, 22: 53-63. 10.1006/biol.1994.1008.

PubMedGoogle Scholar

Didierlaurent AM, Morel S, Lockman L, Giannini SL, Bisteau M, Carlsen H, Kielland A, Vosters O, Vanderheyde N, Schiavetti F: AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity. J Immunol. 2009, 183: 6186-6197. 10.4049/jimmunol.0901474.

PubMedGoogle Scholar

Kuroda E, Coban C, Ishii KJ: Particulate adjuvant and innate immunity: past achievements, present findings, and future prospects. Int Rev Immunol. 2013, 32: 209-220. 10.3109/08830185.2013.773326.

PubMedCentralPubMedGoogle Scholar

Hutchison S, Benson RA, Gibson VB, Pollock AH, Garside P, Brewer JM: Antigen depot is not required for alum adjuvanticity. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2012, 26: 1272-1279. 10.1096/fj.11-184556.

Google Scholar

Lambrecht BN, Kool M, Willart MA, Hammad H: Mechanism of action of clinically approved adjuvants. Curr Opin Immunol. 2009, 21: 23-29. 10.1016/j.coi.2009.01.004.

PubMedGoogle Scholar

Brewer JM: (How) do aluminium adjuvants work?. Immunol Lett. 2006, 102: 10-15. 10.1016/j.imlet.2005.08.002.

PubMedGoogle Scholar

Edelman R: Vaccine adjuvants. Rev Infect Dis. 1980, 2: 370-383. 10.1093/clinids/2.3.370.

PubMedGoogle Scholar

Shoenfeld Y, Agmon-Levin N: ‘ASIA’ - autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011, 36: 4-8. 10.1016/j.jaut.2010.07.003.

PubMedGoogle Scholar

O’Hagan DT, Ott GS, De Gregorio E, Seubert A: The mechanism of action of MF59 - an innately attractive adjuvant formulation. Vaccine. 2012, 30: 4341-4348. 10.1016/j.vaccine.2011.09.061.

PubMedGoogle Scholar

Bernewitz R, Guthausen G, Schuchmann HP: NMR on emulsions: characterisation of liquid dispersed systems. Magnetic resonance in chemistry: MRC. 2011, 49 (Suppl 1): S93-S104.

PubMedGoogle Scholar

Cheetangdee N, Oki M, Fukada K: The coalescence stability of protein-stabilized emulsions estimated by analytical photo-centrifugation. Journal of oleo science. 2011, 60: 419-427. 10.5650/jos.60.419.

PubMedGoogle Scholar

Dupuis M, Murphy TJ, Higgins D, Ugozzoli M, van Nest G, Ott G, McDonald DM: Dendritic cells internalize vaccine adjuvant after intramuscular injection. Cell Immunol. 1998, 186: 18-27. 10.1006/cimm.1998.1283.

PubMedGoogle Scholar

Ott G, Barchfeld GL, Chernoff D, Radhakrishnan R, van Hoogevest P, Van Nest G: MF59. Design and evaluation of a safe and potent adjuvant for human vaccines. Pharm Biotechnol. 1995, 6: 277-296. 10.1007/978-1-4615-1823-5_10.

PubMedGoogle Scholar

Carlson BC, Jansson AM, Larsson A, Bucht A, Lorentzen JC: The endogenous adjuvant squalene can induce a chronic T-cell-mediated arthritis in rats. The American journal of pathology. 2000, 156: 2057-2065. 10.1016/S0002-9440(10)65077-8.

PubMedCentralPubMedGoogle Scholar

Durando P, Icardi G, Ansaldi F: MF59-adjuvanted vaccine: a safe and useful tool to enhance and broaden protection against seasonal influenza viruses in subjects at risk. Expert opinion on biological therapy. 2010, 10: 639-651. 10.1517/14712591003724662.

PubMedGoogle Scholar

Partinen M, Saarenpaa-Heikkila O, Ilveskoski I, Hublin C, Linna M, Olsen P, Nokelainen P, Alen R, Wallden T, Espo M: Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland. PloS one. 2012, 7: e33723-10.1371/journal.pone.0033723.

PubMedCentralPubMedGoogle Scholar

Nohynek H, Jokinen J, Partinen M, Vaarala O, Kirjavainen T, Sundman J, Himanen SL, Hublin C, Julkunen I, Olsen P: AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland. PloS one. 2012, 7: e33536-10.1371/journal.pone.0033536.

PubMedCentralPubMedGoogle Scholar

Mahlios J, De la Herran-Arita AK, Mignot E: The autoimmune basis of narcolepsy. Current opinion in neurobiology. 2013, 767-773.

Google Scholar

Hirschfeld M, Ma Y, Weis JH, Vogel SN, Weis JJ: Cutting edge: repurification of lipopolysaccharide eliminates signaling through both human and murine toll-like receptor 2. J Immunol. 2000, 165: 618-622.

PubMedGoogle Scholar

Tapping RI, Akashi S, Miyake K, Godowski PJ, Tobias PS: Toll-like receptor 4, but not toll-like receptor 2, is a signaling receptor for Escherichia and Salmonella lipopolysaccharides. J Immunol. 2000, 165: 5780-5787.

PubMedGoogle Scholar

Evans JT, Cluff CW, Johnson DA, Lacy MJ, Persing DH, Baldridge JR: Enhancement of antigen-specific immunity via the TLR4 ligands MPL adjuvant and Ribi.529. Expert review of vaccines. 2003, 2: 219-229. 10.1586/14760584.2.2.219.

PubMedGoogle Scholar

Martin M, Michalek SM, Katz J: Role of innate immune factors in the adjuvant activity of monophosphoryl lipid A. Infect Immun. 2003, 71: 2498-2507. 10.1128/IAI.71.5.2498-2507.2003.

PubMedCentralPubMedGoogle Scholar

Tiberio L, Fletcher L, Eldridge JH, Duncan DD: Host factors impacting the innate response in humans to the candidate adjuvants RC529 and monophosphoryl lipid A. Vaccine. 2004, 22: 1515-1523. 10.1016/j.vaccine.2003.10.019.

PubMedGoogle Scholar

Verstraeten T, Descamps D, David MP, Zahaf T, Hardt K, Izurieta P, Dubin G, Breuer T: Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines. Vaccine. 2008, 26: 6630-6638. 10.1016/j.vaccine.2008.09.049.

PubMedGoogle Scholar

Chen WC, Huang L: Non-viral vector as vaccine carrier. Adv Genet. 2005, 54: 315-337.

PubMedGoogle Scholar

Daemen T, de Mare A, Bungener L, de Jonge J, Huckriede A, Wilschut J: Virosomes for antigen and DNA delivery. Advanced drug delivery reviews. 2005, 57: 451-463. 10.1016/j.addr.2004.09.005.

PubMedGoogle Scholar

Immordino ML, Dosio F, Cattel L: Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine. 2006, 1: 297-315. 10.2217/17435889.1.3.297.

PubMedCentralPubMedGoogle Scholar

Flower DR: Chapter 9 - towards the systematic discovery of immunomodulatory adjuvants. Immunomic Discovery of Adjuvants and Candidate Subunit Vaccines, Immunocomics Reviews. 2013, 155-180.

Google Scholar

Lillehoj HS, Ding X, Dalloul RA, Sato T, Yasuda A, Lillehoj EP: Embryo vaccination against Eimeria tenella and E. acervulina infections using recombinant proteins and cytokine adjuvants. J Parasitol. 2005, 91: 666-673. 10.1645/GE-3476.

PubMedGoogle Scholar

Solmesky LJ, Shuman M, Goldsmith M, Weil M, Peer D: Assessing cellular toxicities in fibroblasts upon exposure to lipid-based nanoparticles: a high content analysis approach. Nanotechnology. 2011, 22: 494016-10.1088/0957-4484/22/49/494016.

PubMedGoogle Scholar

Landesman-Milo D, Goldsmith M, Leviatan Ben-Arye S, Witenberg B, Brown E, Leibovitch S, Azriel S, Tabak S, Morad V, Peer D: Hyaluronan grafted lipid-based nanoparticles as RNAi carriers for cancer cells. Cancer letters. 2013, 334: 221-227. 10.1016/j.canlet.2012.08.024.

PubMedGoogle Scholar

Korsholm KS, Andersen PL, Christensen D: Cationic liposomal vaccine adjuvants in animal challenge models: overview and current clinical status. Expert review of vaccines. 2012, 11: 561-577. 10.1586/erv.12.22.

PubMedGoogle Scholar

Smith LR, Wloch MK, Ye M, Reyes LR, Boutsaboualoy S, Dunne CE, Chaplin JA, Rusalov D, Rolland AP, Fisher CL: Phase 1 clinical trials of the safety and immunogenicity of adjuvanted plasmid DNA vaccines encoding influenza A virus H5 hemagglutinin. Vaccine. 2010, 28: 2565-2572. 10.1016/j.vaccine.2010.01.029.

PubMedGoogle Scholar

Safety and Immunogenicity Study of Intramuscular CCS/C-adjuvanted Influenza Vaccine in Elderly. [http://clinicaltrials.gov/ct2/show/NCT00915187?term=NCT00915187&rank=1] []

Christensen D, Agger EM, Andreasen LV, Kirby D, Andersen P, Perrie Y: Liposome-based cationic adjuvant formulations (CAF): past, present, and future. Journal of liposome research. 2009, 19: 2-11. 10.1080/08982100902726820.

PubMedGoogle Scholar

Schoenen H, Bodendorfer B, Hitchens K, Manzanero S, Werninghaus K, Nimmerjahn F, Agger EM, Stenger S, Andersen P, Ruland J: Cutting edge: mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate. J Immunol. 2010, 184: 2756-2760. 10.4049/jimmunol.0904013.

PubMedCentralPubMedGoogle Scholar

Christensen D, Henriksen-Lacey M, Kamath AT, Lindenstrom T, Korsholm KS, Christensen JP, Rochat AF, Lambert PH, Andersen P, Siegrist CA: A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog. Journal of controlled release: official journal of the Controlled Release Society. 2012, 160: 468-476. 10.1016/j.jconrel.2012.03.016.

Google Scholar

Schellack C, Prinz K, Egyed A, Fritz JH, Wittmann B, Ginzler M, Swatosch G, Zauner W, Kast C, Akira S: IC31, a novel adjuvant signaling via TLR9, induces potent cellular and humoral immune responses. Vaccine. 2006, 24: 5461-5472. 10.1016/j.vaccine.2006.03.071.

PubMedGoogle Scholar

Hemmi H, Kaisho T, Takeda K, Akira S: The roles of toll-like receptor 9, MyD88, and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets. J Immunol. 2003, 170: 3059-3064.

PubMedGoogle Scholar

Weeratna RD, Brazolot Millan CL, McCluskie MJ, Davis HL: CpG ODN can re-direct the Th bias of established Th2 immune responses in adult and young mice. FEMS Immunol Med Microbiol. 2001, 32: 65-71. 10.1111/j.1574-695X.2001.tb00535.x.

PubMedGoogle Scholar

Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S: A toll-like receptor recognizes bacterial DNA. Nature. 2000, 408: 740-745. 10.1038/35047123.

PubMedGoogle Scholar

Heeg K, Zimmermann S: CpG DNA as a Th1 trigger. Int Arch Allergy Immunol. 2000, 121: 87-97. 10.1159/000024303.

PubMedGoogle Scholar

Silva BD, da Silva EB, Do Nascimento IP, dos Reis MCG, Kipnis A, Junqueira-Kipnis AP: MPT-51/CpG DNA vaccine protects mice against mycobacterium tuberculosis. Vaccine. 2009, 27: 4402-4407. 10.1016/j.vaccine.2009.05.049.

PubMedGoogle Scholar

Wu F, Yuan XY, Li J, Chen YH: The co-administration of CpG-ODN influenced protective activity of influenza M2e vaccine. Vaccine. 2009, 27: 4320-4324. 10.1016/j.vaccine.2009.04.075.

PubMedGoogle Scholar

Jalilian B, Omar A, Bejo M, Alitheen N, Rasoli M, Matsumoto S: Development of avian influenza virus H5 DNA vaccine and MDP-1 gene of mycobacterium bovis as genetic adjuvant. Genetic Vaccines and Therapy. 2010, 8: 4-10.1186/1479-0556-8-4.

PubMedCentralPubMedGoogle Scholar

Oveissi S, Omar AR, Yusoff K, Jahanshiri F, Hassan SS: DNA vaccine encoding avian influenza virus H5 and Esat-6 of mycobacterium tuberculosis improved antibody responses against AIV in chickens. Comp Immunol Microbiol Infect Dis. 2010, 33: 491-503. 10.1016/j.cimid.2009.08.004.

PubMedGoogle Scholar

Noessner E, Gastpar R, Milani V, Brandl A, Hutzler PJS, Kuppner MC, Roos M, Kremmer E, Asea A, Calderwood SK, Issels RD: Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells. J Immunol. 2002, 169: 5424-5432.

PubMedGoogle Scholar

Udono H, Yamano T, Kawabata Y, Ueda M, Yui K: Generation of cytotoxic T lymphocytes by MHC class I ligands fused to heat shock cognate protein 70. Int Immunol. 2001, 13: 1233-1242. 10.1093/intimm/13.10.1233.

PubMedGoogle Scholar

Li J, Ye ZX, Li KN, Cui JH, Cao YX, Liu YF, Yang SJ: HSP70 gene fused with hantavirus S segment DNA significantly enhances the DNA vaccine potency against hantaviral nucleocapsid protein in vivo. Vaccine. 2007, 25: 239-252. 10.1016/j.vaccine.2006.07.040.

PubMedGoogle Scholar

Qazi KR, Wikman M, Vasconcelos NM, Berzins K, StaÃähl S, FernaÃÅndez C: Enhancement of DNA vaccine potency by linkage of plasmodium falciparum malarial antigen gene fused with a fragment of HSP70 gene. Vaccine. 2005, 23: 1114-1125. 10.1016/j.vaccine.2004.08.033.

PubMedGoogle Scholar

Fox CB, Kramer RM, Barnes VL, Dowling QM, Vedvick TS: Working together: interactions between vaccine antigens and adjuvants. Ther Adv Vaccines. 2013, 1: 7-20.

PubMedCentralPubMedGoogle Scholar

Dufort S, Sancey L, Coll JL: Physico-chemical parameters that govern nanoparticles fate also dictate rules for their molecular evolution. Advanced drug delivery reviews. 2012, 64: 179-189. 10.1016/j.addr.2011.09.009.

PubMedGoogle Scholar

Vorup-Jensen T, Boesen T: Protein ultrastructure and the nanoscience of complement activation. Advanced drug delivery reviews. 2011, 63: 1008-1019. 10.1016/j.addr.2011.05.023.

PubMedGoogle Scholar

Holmskov U, Thiel S, Jensenius JC: Collections and ficolins: humoral lectins of the innate immune defense. Annual review of immunology. 2003, 21: 547-578. 10.1146/annurev.immunol.21.120601.140954.

PubMedGoogle Scholar

Carroll MC, Isenman DE: Regulation of humoral immunity by complement. Immunity. 2012, 37: 199-207. 10.1016/j.immuni.2012.08.002.

PubMedGoogle Scholar

Gonzalez SF, Degn SE, Pitcher LA, Woodruff M, Heesters BA, Carroll MC: Trafficking of B cell antigen in lymph nodes. Annual review of immunology. 2011, 29: 215-233. 10.1146/annurev-immunol-031210-101255.

PubMedGoogle Scholar

Heesters BA, Chatterjee P, Kim YA, Gonzalez SF, Kuligowski MP, Kirchhausen T, Carroll MC: Endocytosis and recycling of immune complexes by follicular dendritic cells enhances B cell antigen binding and activation. Immunity. 2013, 38: 1164-1175. 10.1016/j.immuni.2013.02.023.

PubMedCentralPubMedGoogle Scholar

Fearon DT, Locksley RM: The instructive role of innate immunity in the acquired immune response. Science. 1996, 272: 50-54. 10.1126/science.272.5258.50.

PubMedGoogle Scholar

Watanabe I, Ross TM, Tamura S, Ichinohe T, Ito S, Takahashi H, Sawa H, Chiba J, Kurata T, Sata T, Hasegawa H: Protection against influenza virus infection by intranasal administration of C3d-fused hemagglutinin. Vaccine. 2003, 21: 4532-4538. 10.1016/S0264-410X(03)00510-3.

PubMedGoogle Scholar

Mkrtichyan M, Ghochikyan A, Movsesyan N, Karapetyan A, Begoyan G, Yu J, Glenn GM, Ross TM, Agadjanyan MG, Cribbs DH: Immunostimulant adjuvant patch enhances humoral and cellular immune responses to DNA immunization. DNA and cell biology. 2008, 27: 19-24. 10.1089/dna.2007.0639.

PubMedCentralPubMedGoogle Scholar

Moghimi SM, Hunter AC, Andresen TL: Factors controlling nanoparticle pharmacokinetics: an integrated analysis and perspective. Annual review of pharmacology and toxicology. 2012, 52: 481-503. 10.1146/annurev-pharmtox-010611-134623.

PubMedGoogle Scholar

Szebeni J, Muggia F, Gabizon A, Barenholz Y: Activation of complement by therapeutic liposomes and other lipid excipient-based therapeutic products: prediction and prevention. Advanced drug delivery reviews. 2011, 63: 1020-1030. 10.1016/j.addr.2011.06.017.

PubMedGoogle Scholar

Batrakova EV, Kabanov AV: Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers. Journal of controlled release: official journal of the Controlled Release Society. 2008, 130: 98-106. 10.1016/j.jconrel.2008.04.013.

Google Scholar

Hamad I, Hunter AC, Moghimi SM: Complement monitoring of pluronic 127 gel and micelles: suppression of copolymer-mediated complement activation by elevated serum levels of HDL, LDL, and apolipoproteins AI and B-100. Journal of controlled release: official journal of the Controlled Release Society. 2013, 170: 167-174. 10.1016/j.jconrel.2013.05.030.

Google Scholar

Hartikka J, Geall A, Bozoukova V, Kurniadi D, Rusalov D, Enas J, Yi JH, Nanci A, Rolland A: Physical characterization and in vivo evaluation of poloxamer-based DNA vaccine formulations. The journal of gene medicine. 2008, 10: 770-782. 10.1002/jgm.1199.

PubMedGoogle Scholar

Pedersen MB, Zhou X, Larsen EK, Sorensen US, Kjems J, Nygaard JV, Nyengaard JR, Meyer RL, Boesen T, Vorup-Jensen T: Curvature of synthetic and natural surfaces is an important target feature in classical pathway complement activation. J Immunol. 2010, 184: 1931-1945. 10.4049/jimmunol.0902214.

PubMedGoogle Scholar

Klein CP, de Groot K, Vermeiden JP, van Kamp G: Interaction of some serum proteins with hydroxylapatite and other materials. Journal of biomedical materials research. 1980, 14: 705-712. 10.1002/jbm.820140602.

PubMedGoogle Scholar

Tengvall P, Askendal A, Lundstrom I: Studies on protein adsorption and activation of complement on hydrated aluminium surfaces in vitro. Biomaterials. 1998, 19: 935-940. 10.1016/S0142-9612(98)00005-2.

PubMedGoogle Scholar

Pacheco PM, Le B, White D, Sulchek T: Tunable complement activation by particles with variable size and Fc density. Nano LIFE. 2013, 3: 1341001-1341012. 10.1142/S1793984413410018.

PubMedCentralPubMedGoogle Scholar

Moghimi SM, Hamad I, Andresen TL, Jorgensen K, Szebeni J: Methylation of the phosphate oxygen moiety of phospholipid-methoxy(polyethylene glycol) conjugate prevents PEGylated liposome-mediated complement activation and anaphylatoxin production. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2006, 20: 2591-2593. 10.1096/fj.06-6186fje.

Google Scholar

Thielens NM, Tacnet-Delorme P, Arlaud GJ: Interaction of C1q and mannan-binding lectin with viruses. Immunobiology. 2002, 205: 563-574. 10.1078/0171-2985-00155.

PubMedGoogle Scholar

auf dem Keller U, Prudova A, Eckhard U, Fingleton B, Overall CM: Systems-level analysis of proteolytic events in increased vascular permeability and complement activation in skin inflammation. Science signaling. 2013, 6: rs2-10.1126/scisignal.2003512.

PubMedGoogle Scholar

Heimlich JM, Regnier FE, White JL, Hem SL: The in vitro displacement of adsorbed model antigens from aluminium-containing adjuvants by interstitial proteins. Vaccine. 1999, 17: 2873-2881. 10.1016/S0264-410X(99)00126-7.

PubMedGoogle Scholar

Deng ZJ, Liang M, Monteiro M, Toth I, Minchin RF: Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation. Nature nanotechnology. 2011, 6: 39-44. 10.1038/nnano.2010.250.

PubMedGoogle Scholar

Vorup-Jensen T, Carman CV, Shimaoka M, Schuck P, Svitel J, Springer TA: Exposure of acidic residues as a danger signal for recognition of fibrinogen and other macromolecules by integrin alphaXbeta2. Proc Natl Acad Sci USA. 2005, 102: 1614-1619. 10.1073/pnas.0409057102.

PubMedCentralPubMedGoogle Scholar

Nakashima Y, Sun DH, Trindade MC, Maloney WJ, Goodman SB, Schurman DJ, Smith RL: Signaling pathways for tumor necrosis factor-alpha and interleukin-6 expression in human macrophages exposed to titanium-alloy particulate debris in vitro. The Journal of bone and joint surgery American volume. 1999, 81: 603-615.

PubMedGoogle Scholar

Schuck P, Zhao H: The role of mass transport limitation and surface heterogeneity in the biophysical characterization of macromolecular binding processes by SPR biosensing. Methods Mol Biol. 2010, 627: 15-54. 10.1007/978-1-60761-670-2_2.

PubMedCentralPubMedGoogle Scholar

Aderem A, Underhill DM: Mechanisms of phagocytosis in macrophages. Annual review of immunology. 1999, 17: 593-623. 10.1146/annurev.immunol.17.1.593.

PubMedGoogle Scholar

Zhang S, Li J, Lykotrafitis G, Bao G, Suresh S: Size-Dependent Endocytosis of Nanoparticles. Adv Mater. 2009, 21: 419-424. 10.1002/adma.200801393.

PubMedCentralPubMedGoogle Scholar

Rabinovitch M: Professional and non-professional phagocytes: an introduction. Trends in cell biology. 1995, 5: 85-87. 10.1016/S0962-8924(00)88955-2.

PubMedGoogle Scholar

Huang C, Zhang Y, Yuan H, Gao H, Zhang S: Role of nanoparticle geometry in endocytosis: laying down to stand up. Nano letters. 2013

Google Scholar

Tollis S, Dart AE, Tzircotis G, Endres RG: The zipper mechanism in phagocytosis: energetic requirements and variability in phagocytic cup shape. BMC systems biology. 2010, 4: 149-10.1186/1752-0509-4-149.

PubMedCentralPubMedGoogle Scholar

Swanson JA: Shaping cups into phagosomes and macropinosomes. Nature reviews Molecular cell biology. 2008, 9: 639-649. 10.1038/nrm2447.

PubMedCentralPubMedGoogle Scholar

Li J, Barreda DR, Zhang YA, Boshra H, Gelman AE, Lapatra S, Tort L, Sunyer JO: B lymphocytes from early vertebrates have potent phagocytic and microbicidal abilities. Nature immunology. 2006, 7: 1116-1124. 10.1038/ni1389.

PubMedGoogle Scholar

Doolittle RF, Yang Z, Mochalkin I: Crystal structure studies on fibrinogen and fibrin. Ann N Y Acad Sci. 2001, 936: 31-43.

PubMedGoogle Scholar

Xie C, Zhu J, Chen X, Mi L, Nishida N, Springer TA: Structure of an integrin with an alphaI domain, complement receptor type 4. The EMBO journal. 2010, 29: 666-679. 10.1038/emboj.2009.367.

PubMedCentralPubMedGoogle Scholar

Published
2013-11-06
Section
Review

Most read articles by the same author(s)